Acetazolamide in Central Sleep Apnea Patients Using Medication for Opioid Use Disorder

June 22, 2026 updated by: Sanjay R Patel

Impact of Acetazolamide on Central Sleep Apnea Patients Receiving Medication for Opioid Use Disorder

Patients with opioid use disorder treated with either methadone or buprenorphine are at risk of developing central sleep apnea (CSA) from these medications. Investigators will conduct a mechanistic trial using acetazolamide, a medicine known to improve CSA in other settings, to determine if acetazolamide can improve CSA due to medication for opioid use disorder and whether this leads to physiologic changes that might lead to reduced drug craving. Patients treated with medication for opioid use disorder and who have central sleep apnea will be randomized to treatment with acetazolamide or matching placebo for 7 days. At the end of the 7 days, they will undergo an overnight sleep study to assess the impact on breathing during sleep as well as sleep quality. In addition, measures of sympathetic tone, anxiety, arousal, cognition, and drug craving will be measured to determine if treatment of CSA with acetazolamide can produce physiologic changes that might contribute to improved health.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Medications used to treat opioid use disorder (MOUD) such as methadone and buprenorphine have been found to cause central sleep apnea (CSA), but the clinical ramifications are unclear. It has been hypothesized that the sleep fragmentation and intermittent hypoxemia caused by CSA from MOUD may lead to sympathetic activation, nocturnal arousal, increased anxiety, and cognitive impairment that may in turn increase drug craving and drug relapse. This mechanistic study will evaluate the potential adverse effect of CSA in patients on MOUD by evaluating the impact of acetazolamide to improve CSA and thereby lead to downstream physiologic changes in measures of sleep quality, sympathetic tone, nocturnal arousal, anxiety, cognitive functioning, and drug craving.

Eligible individuals will undergo an overnight research visit including overnight polysomnography, assessments of autonomic tone, sleep quality, nocturnal arousal, emotional distress, cognitive testing, and drug craving. Individuals with opioid-induced CSA will be randomized into a parallel-arm trial of acetazolamide vs. placebo with overnight research visit for outcome assessment at 7 days.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh
        • Principal Investigator:
          • Sanjay R Patel, MD
        • Sub-Investigator:
          • Venkatesh Krishnamurthy, MD
        • Sub-Investigator:
          • Tae Woo Park, MD
        • Sub-Investigator:
          • Kristine Wilckens, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients on Medication for Opioid Use Disorder (MOUD) with central sleep apnea.

Exclusion Criteria:

  • Sleep-related Hypoventilation.
  • Other causes of Central Sleep Apnea besides Opioid Use.
  • Pregnancy.
  • Contraindications for Acetazolamide.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acetazolamide
All participants in this group will receive one acetazolamide 250 mg pill in the evening for 7 days.
Drug: Acetazolamide
Oral acetazolamide 250 mg daily for 7 days
Placebo Comparator: Placebo
All participants in this group will receive one matching placebo pill in the evening for 7 days.
Drug: Placebo
Oral placebo daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central Apnea Index (CAI)
Time Frame: 7 days

The number of central apneas per hour of sleep, assessed by overnight polysomnography.

  • It can range from 0 to undefined events per hour.
  • Higher values indicate more severe central sleep apnea.
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Low frequency / high-frequency ratio (LF/HF ratio)
Time Frame: 7 days
The ratio of low frequency to high frequency spectral power from heart rate variability analysis of electrocardiogram (ECG) collected during non-rapid eye movement (NREM) sleep on overnight polysomnography
7 days
Apnea Hypopnea Index (AHI)
Time Frame: 7 days

The number of apneas plus hypopneas per hour of sleep on overnight polysomnography

  • It can range from 0 to undefined events per hour.
  • Higher values indicates severity of apneas and hypopneas.
7 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overnight urinary norepinephrine levels
Time Frame: 7 days
Overnight urinary norepinephrine concentration normalized to urinary creatinine concentration
7 days
Pre-ejection period
Time Frame: 7 days
Pre-ejection period assessed by impedance cardiography
7 days
Pre-sleep Arousal Scale (PSAS) score
Time Frame: 7 days

16-item questionnaire assessing level of nocturnal arousal

  • It can range from 16 to 80.
  • Higher scores indicate higher levels of nocturnal arousal.
7 days
Arousal Index
Time Frame: 7 days

The number of cortical arousals per hour of sleep on overnight polysomnography.

  • It can range from 0 to undefined events per hour.
  • Higher values indicate more severe sleep disturbance.
7 days
Generalized Anxiety Disorder 7 (GAD-7) score
Time Frame: 7 days

7-item questionnaire assessing anxiety symptoms

  • It can range from 0 to 21.
  • Higher scores indicate more severe anxiety.
7 days
Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance score
Time Frame: 7 days

t-score derived from 8-item PROMIS sleep disturbance questionnaire

  • Population mean is 50 and standard deviation is 10.
  • Higher values indicate greater levels of sleep disturbance.
7 days
Opioid cue-induced drug craving
Time Frame: 7 days

The mean craving score reported after exposure to visual opioid cues relative to craving scores after viewing neutral cues.

  • Mean craving score ranges from 0 to 10.
  • Higher scores indicate higher level of drug craving.
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanjay R Patel

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Sanjay R Patel, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2025

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

July 19, 2024

First Submitted That Met QC Criteria

July 19, 2024

First Posted (Actual)

July 26, 2024

Study Record Updates

Last Update Posted (Actual)

June 25, 2026

Last Update Submitted That Met QC Criteria

June 22, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY23100016
  • R01DA059465 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual Participant Data (IPD) from this clinical trial will be shared with other researchers. The IPD to be shared includes final closed dataset (after de-identification). All data will be released according to the specific timelines stated in the National Institutes of Health (NIH) Policy, ensuring no compromise to privacy, confidentiality, proprietary interests, national security, or law enforcement activities. These data will be submitted to a NIH-funded data registry for data sharing purposes.

IPD Sharing Time Frame

The IPD will become available within 1 year of analysis of primary outcome. This data will be accessible on an NIH-sponsored platform for as long as the agency maintains it.

IPD Sharing Access Criteria

IPD will be available through a NIH funded registry. Access to the IPD will be governed by the policies and procedures of NIH.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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